A basic challenge for biotechnology is to develop approaches for delivering genetic information to cells in vivo. The purposeful delivery of genetic material to somatic cells for the purpose of treating disease or for biomedical investigation has been termed gene therapy. Gene therapy promises to be a significant advance in the treatment of infections as well as somatic and hereditary genetic diseases. To be successful, the polynucleotide must be delivered to a therapeutically significant percentage of the affected cells in a manner that is both efficient and safe. The delivered polynucleotide can then compensate for a missing endogenous gene, provide a beneficial function or block activity of a dominant negative endogenous gene or gene of an infectious organism. If genetic materials are appropriately delivered to a patient they can potentially enhance a patient's health and, in some instances, lead to a cure. Specifically, the development of methods for gene transfer into the prostate is attractive given that prostate cancer is a leading cause of morbidity and mortality in men and has a stronger hereditary component than any other type of cancer. Most prostate tumors arise from the secretory epithelial cells that line the lumenal surface of the prostatic ducts and acini. It has been recognized that gene therapy could offer a new tool in the battle against this cancer. Delivery of genes to prostate in animal models will also further biomedical research into the causes, mechanisms and potential treatments of enlarged prostate, prostate cancer and benign prostatic hyperplasia.
It was first observed that the in vivo injection of plasmid DNA into muscle enabled the expression of foreign genes in muscle cells near the point of injection [Wolff et al. 1990]. Since that report, several other studies have reported foreign gene expression following the direct injection of DNA into the parenchyma of other tissues. Transfection following direct injection has been observed for: cardiac muscle [Acsadi et al 1991], pig epidermis [Hengge et al. 1995], rabbit thyroid [Sikes et al. 1994], melanoma tumors [Vile et al. 1993], rat liver [Malone et al. 1994, Hickman 1994] lung by intratracheal injection [Meyer et al. 1995], and into arteries using a hydrogel-coated angioplasty balloon [Riessen et al. 1993, Chapman et al. 1992]. A number of other techniques have also been explored for delivery of polynucleotides to cells in mammals. These techniques include the “gene gun” method, electroporation, the use of viral vectors, and cationic liposome and polymer transfection reagents. However, each of these techniques suffer from delivery to too few cells and/or toxicity. For instance, cationic DNA-containing complexes are highly effective in vitro but generally have been of limited success in vivo because the complexes are typically too large and their positive charge has an adverse influence on biodistribution.